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Considerations for Certain Concomitant Medications in Patients with COVID-19

Last Updated: June 25, 2020

Summary Recommendations
Summary Recommendations

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs):

  • Persons with COVID-19 who are prescribed ACE inhibitors or ARBs for cardiovascular disease (or other indications) should continue these medications (AIII).
  • The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of ACE inhibitors or ARBs for the treatment of COVID-19 outside of the setting of a clinical trial (AIII).

Corticosteroids

For Management of COVID-19:

  • The Panel recommends using dexamethasone (at a dose of 6 mg per day for up to 10 days) in patients with COVID-19 who are mechanically ventilated (AI) and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated (BI).
  • The Panel recommends against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen (AI).
  • See the Panel’s guidance on the use of dexamethasone for a detailed discussion of these recommendations.

For Patients on Chronic Corticosteroids:

  • Oral corticosteroid therapy that was used prior to COVID-19 diagnosis for another underlying condition (e.g., primary or secondary adrenal insufficiency, rheumatological diseases) should not be discontinued (AIII). On a case-by-case basis, supplemental or stress-dose steroids may be indicated (AIII).
  • Inhaled corticosteroids that are used daily for patients with asthma and chronic obstructive pulmonary disease for control of airway inflammation should not be discontinued in patients with COVID-19 (AIII).
Pregnancy Considerations:
  • The antenatal corticosteroids betamethasone and dexamethasone are known to cross the placenta and are therefore generally reserved for when administration is required for fetal benefit (BIII). Other systemic corticosteroids do not cross the placenta, and pregnancy is not a reason to restrict their use if otherwise indicated (CIII).
  • Modifications to care for these patients and the use of corticosteroids that cross the placenta may be individualized, weighing the neonatal and maternal benefits of antenatal corticosteroid use with the risks of potential harm (CIII).

HMG-CoA Reductase Inhibitors (Statins):

  • Persons with COVID-19 who are prescribed statin therapy for the treatment or prevention of cardiovascular disease should continue these medications (AIII).
  • The Panel recommends against the use of statins for the treatment of COVID-19 outside the setting of a clinical trial (AIII).

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs):

  • Persons with COVID-19 who are taking NSAIDs for a comorbid condition should continue therapy as previously directed by their physician (AIII).
  • The Panel recommends that there be no difference in the use of antipyretic strategies (e.g., with acetaminophen or NSAIDs) between patients with or without COVID-19 (AIII).

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers

Recommendations

  • Persons with COVID-19 who are prescribed angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for cardiovascular disease (or other indications) should continue these medications (AIII).
  • The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of ACE inhibitors or ARBs for the treatment of COVID-19 outside the setting of a clinical trial (AIII).

Angiotensin-converting enzyme 2 (ACE2) is the cell surface receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been hypothesized1 that the modulation of ACE2 associated with these therapies could suppress or enhance SARS-CoV-2 replication.2 Investigations of the role of ARBs and recombinant human ACE2 in treatment and prevention of SARS-CoV-2 infection are underway.3

Whether these medications are helpful, harmful, or neutral in the pathogenesis of SARS-CoV-2 infection is unclear. Currently, there is a lack of sufficient clinical evidence demonstrating that ACE inhibitors or ARBs have any impact on the susceptibility of individuals to SARS-CoV-2 or on the severity or outcomes of infection. This recommendation is in accord with a joint statement of the American Heart Association, the Heart Failure Society of America, and the American College of Cardiology.3

Corticosteroids

It has been proposed that the anti-inflammatory effects of corticosteroids have a potential therapeutic role in suppressing cytokine-related lung injury in patients with COVID-19.4 Data from other respiratory infections have shown that systemic corticosteroids can affect the pathogenesis of these infections in various ways. In outbreaks of other novel coronavirus infections5,6 (i.e., Middle East respiratory syndrome [MERS] and severe acute respiratory syndrome [SARS]), corticosteroid therapy was associated with delayed virus clearance. In severe pneumonia caused by influenza, corticosteroid therapy may worsen clinical outcomes, including secondary bacterial infection and mortality.7

Preliminary clinical trial data from a large, randomized, open-label trial suggest that dexamethasone reduces mortality in hospitalized patients with COVID-19 who require mechanical ventilation or supplemental oxygen.8 The recommendations for using corticosteroids in patients with COVID-19 depend on the severity of illness. Before initiating dexamethasone, clinicians should review the patient’s medical history and assess the potential risks and benefits of administering corticosteroids to the patient.

For Management of COVID-19

  • The Panel recommends using dexamethasone (at a dose of 6 mg per day for up to 10 days) in patients with COVID-19 who are mechanically ventilated (AI) and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated (BI).
  • The Panel recommends against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen (AI).

See the Panel’s guidance on the use of dexamethasone for a detailed discussion of these recommendations.

Patients on Chronic Systemic Corticosteroid Therapy

Patients with COVID-19 may also be receiving systemic corticosteroid therapy for a variety of underlying conditions.

Recommendation

  • Oral corticosteroid therapy that was used prior to COVID-19 diagnosis for another underlying condition (e.g., primary or secondary adrenal insufficiency, rheumatological diseases) should not be discontinued (AIII).9 On a case-by-case basis, supplemental or stress-dose steroids may be indicated (AIII).

Patients on Inhaled Corticosteroids

Recommendation

  • Inhaled corticosteroids that are used daily for patients with asthma and chronic obstructive pulmonary disease for control of airway inflammation should not be discontinued in patients with COVID-19 (AIII). No studies to date have investigated the relationship between inhaled corticosteroids in these settings and virus acquisition, severity of illness, or viral transmission.

Pregnancy Considerations

The antenatal corticosteroids betamethasone and dexamethasone are known to cross the placenta and are therefore generally reserved for when administration is required for fetal benefits (BIII). Other systemic corticosteroids do not cross the placenta, and pregnancy is not a reason to restrict their use if otherwise indicated.10

HMG-CoA Reductase Inhibitors (Statins)

Recommendations

  • Persons with COVID-19 who are prescribed statin therapy for the treatment or prevention of cardiovascular disease should continue these medications (AIII).
  • The Panel recommends against the use of statins for the treatment of COVID-19 outside the setting of a clinical trial (AIII).

HMG-CoA reductase inhibitors, or statins, affect ACE2 as part of their function in reducing endothelial dysfunction. It has been proposed that these agents have a potential role in managing patients with severe COVID-19.11 Observational studies have reported that statin therapy may reduce cardiovascular morbidity in patients admitted with other respiratory infections, such as influenza and bacterial pneumonia.

Nonsteroidal Anti-Inflammatory Drugs

Recommendations

  • Persons with COVID-19 who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) for a comorbid condition should continue therapy as previously directed by their physician (AIII).
  • The Panel recommends that there be no difference in the strategy of antipyretic use (e.g., with acetaminophen or NSAIDs) as in patients with or without COVID-19 (AIII).

In mid-March 2020, news agencies promoted reports that anti-inflammatory drugs may worsen COVID-19. It has been proposed that NSAIDs like ibuprofen can increase the expression of ACE21 and inhibit antibody production.12 Shortly after these reports, the Food and Drug Administration stated that there is no evidence linking the use of NSAIDs with worsening of COVID-19 and advised patients to use NSAIDs as directed.13

References

  1. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020;8(4):e21. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32171062.
  2. Patel AB, Verma A. COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence? JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32208485.
  3. American College of Cardiology. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. 2020. Available at: https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19.
  4. Siddiqi HK, Mehra MR. COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal. The Journal of Heart and Lung Transplantation. 2020. [In Press]. Available at: https://www.jhltonline.org/article/S1053-2498(20)31473-X/fulltext.
  5. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197(6):757-767. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29161116.
  6. Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3(9):e343. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16968120.
  7. Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev. 2016;3:CD010406. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26950335.
  8. Horby P, Shen Lim W, Emberson J, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. medRxiv. 2020;[Preprint]. Available at: https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1.
  9. Kaiser UB, Mirmira RG, Stewart PM. Our response to COVID-19 as endocrinologists and diabetologists. J Clin Endocrinol Metab. 2020;105(5). Available at: https://www.ncbi.nlm.nih.gov/pubmed/32232480.
  10. Resnik R, Lockwood C, Moore T, Greene M, Copel J, Silver R. Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice. 8th Edition. 2018. Elsevier.
  11. Fedson DS, Opal SM, Rordam OM. Hiding in plain sight: an approach to treating patients with severe COVID-19 infection. mBio. 2020;11(2). Available at: https://www.ncbi.nlm.nih.gov/pubmed/32198163.
  12. Bancos S, Bernard MP, Topham DJ, Phipps RP. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol. 2009;258(1):18-28. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19345936.
  13. Food and Drug Administration. FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. 2020. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19. Accessed April 8, 2020.